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Grand Challenges is a family of initiatives fostering innovation to solve key global health and development problems. Each initiative is an experiment in the use of challenges to focus innovation on making an impact. Individual challenges address some of the same problems, but from differing perspectives.

Scientists have long known that only relatively old mosquitoes can transmit the agents that cause certain diseases, including dengue fever and malaria. Dr. O'Neill and his multinational team are working on a plan to shorten the lifespan of mosquitoes that transmit the dengue virus, which infects up to 100 million people each year. They are introducing into populations of Aedes mosquitoes, strains of a naturally occurring bacterial symbiont, Wolbachia, that kill infected insects before they are old enough to transmit disease. Wolbachia are inherited though the eggs of the mosquitoes and so are passed on from generation to generation. O'Neill (Grand Challenges in Global Health: 2005-2015 retrospective)

James DaleQueensland University of TechnologyBrisbane, Queensland, Australia

Grand Challenges in Global Health

Crop Biofortification

1 Jul 2005

Bananas are the major staple food in Uganda, where the average person consumes more than 1 kilogram of the fruit each day. Banana-based diets, however, are deficient in vitamin A and iron, as well as in vitamin E. A promising long-term solution to this problem may be to genetically modify crops, including bananas, so that they contain high levels of essential nutrients. Dr. Dale is leading a team of scientists in Australia, Uganda, and the United States who are attempting to genetically modify bananas raised in Uganda so that their content of vitamin A, vitamin E, and iron is equal to or exceeds the required daily allowance. Dale, Tushemereirwe (Grand Challenges in Global Health: 2005-2015 retrospective)

Vaccinating infants against infectious disease is complicated by newborns' immature immune systems, the tendency of their immune systems to mount Th2-biased responses, and interference from maternal antibodies. Dr. Babiuk's team is working to develop new formulations of vaccines that can induce a long-lasting, balanced immune response in infants after a single­-administration vaccination.

A subset of women who apparently are resistant to HIV infection may provide scientists with the genetic and immune system information they need to advance vaccine and drug development. Since 1985, investigators have tracked groups of commercial sex workers in Kenya who do not become infected with HIV despite repeatedly having sex without condoms. If investigators can understand what constitutes and results in protective immunity against HIV, they may be able to replicate it through vaccines. Dr. Plummer's team is conducting an exhaustive analysis of the immunologic and genetic factors that mediate HIV resistance in the women, with the goal of gaining a more complete understanding of what constitutes protective immunity against HIV infection.

Barton Brett FinlayUniversity of British ColumbiaVancouver, British Columbia, Canada

Grand Challenges in Global Health

Drug Resistance

1 Jul 2005

Dr. Finlay's team is investigating a new approach to treating bacterial and parasitic infections by enhancing the body's innate defense mechanisms. By acting on the cells of the immune system rather than on the disease-causing microbe directly, investigators expect to lessen the risk of developing drug-resistant organisms and the potential for broad-spectrum activity. The project team is focusing on a number of bacterial and parasitic pathogens, including enteric bacteria, Mycobacterium tuberculosis, and Plasmodium falciparum.

Vaccines are urgently needed to slow the spread of HIV and hepatitis C virus (HCV), which together infect an estimated 240 million people, most of them in developing countries. To prepare a human vaccine, investigators need an animal model that can help them screen and prioritize vaccine candidates. Dr. Deng and his colleagues are working to improve techniques for creating mouse models with immune systems and livers that are similar enough to humans to allow testing of potential HIV and HCV vaccines. The team is working to create chimerical mouse models with hematopoietic cells (HSCs) and hepatocytes differentiated from human embryonic stem (hES) cells.

Dr. Jiang’s team is identifying components of human cells that microbes use to establish an infection and replicate but that are not essential to the human host. Better understanding of microbial replication and survival from the view of host cells, the project team anticipates, will provide a foundation for novel therapeutic approaches to combat infectious diseases while simultaneously providing a low likelihood of inducing drug resistance. These compounds could potentially work by interrupting microbes from creating the environment they need to replicate in human cells.

To stop the spread of tuberculosis, scientists are working to develop methods that prevent new infections and also eliminate infection in the huge reservoir of people who already are infected with MTB. New approaches that focus on controlling or stimulating the immune system to cure latent infections or prevent MTB from causing disease have the potential to significantly reduce illness, death, and disease transmission. Dr. Andersen’s is leading a collaborative team of international researchers who are studying Mycobacterium tuberculosis to identify the mechanisms that, in some people, allow it to escape natural immune system responses. The project's ultimate goal is to develop vaccines that target latent TB, either before or after an individual is infected.

Acute respiratory infections, often due to Streptococcus pneumoniae (pneumococcus), are a primary cause of death in young children in developing countries. A new vaccine effectively prevents the most serious form of pneumococcal disease and also reduces nasopharyngeal colonization with pneumococci. Because only some people who are infected become ill, researchers must study tens of thousands of vaccinated individuals over a long period of time to determine whether the vaccine guards against disease. Dr. Käyhty is leading an international consortium of investigators whose goal is to establish a quick and inexpensive method of determining the efficacy and expected effectiveness of the pneumonia vaccine.

Hepatitis C virus (HCV) is a major cause of liver diseases, including cirrhosis and liver cancer. Treatment for chronic hepatitis C is often out of financial reach for people in developing countries, and there is no vaccine against the virus. To prepare a human vaccine, investigators need an animal model that can help them screen and prioritize vaccine candidates. Dr. Balling's team, partnering with Dr. Di Santo's group at the Institut Pasteur in France, is working toward the development of mice with livers and immune systems that are similar to those of humans. These animals might be used to test vaccines for HCV, and potentially, other human pathogens.

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